The DAPA ACT HF-TIMI 68 trial, presented at the 2025 European Society of Cardiology Congress, evaluated the impact of initiating sodium–glucose cotransporter 2 (SGLT2) inhibition during hospitalisation for acute heart failure (HF) on early clinical outcomes.1 This large, multicentre, randomised, double-blind study enrolled 2,401 patients from 23 countries. The mean age was 69 years, and nearly three-quarters (72%) had HF with reduced ejection fraction. Following clinical stabilisation, patients were randomised within 14 days of admission to receive either dapagliflozin 10 mg once daily or placebo, ensuring initiation occurred during the index hospitalisation rather than post-discharge. The primary endpoint, a composite of cardiovascular death or worsening HF, was assessed at 60 days. By evaluating therapy in the acute setting, the trial sought to determine whether earlier initiation could improve short-term outcomes and, potentially, long-term prognosis.
The primary endpoint occurred in 10.9% of patients assigned to dapagliflozin versus 12.7% with placebo (HR 0.86; 95% CI [0.68–1.08]; p=0.20). Although numerically favourable, the difference was not statistically significant. Secondary outcomes showed consistent trends towards benefit, including lower all-cause mortality (3.0% versus 4.5%), fewer worsening HF events, and improved symptom trajectories. Safety was generally acceptable, with slightly higher rates of symptomatic hypotension (3.6% versus 2.2%) and transient renal function decline (5.9% versus 4.7%) in the dapagliflozin group, but no excess of urinary tract infections or ketoacidosis.
When pooled with prior trials of in-hospital SGLT2 initiation in a meta-analysis (~3,500 patients), the findings became more compelling, demonstrating significant reductions in cardiovascular death or worsening HF, as well as all-cause mortality.1,2 This broader evidence base reinforces the clinical relevance of early initiation.
DAPA ACT HF-TIMI 68 confirms that in-hospital initiation of dapagliflozin is feasible, safe, and potentially beneficial.1 However, given the neutral primary endpoint, a universal ‘start-in-all’ recommendation is not justified. The most appropriate approach is selective initiation, particularly in patients with reduced ejection fraction, preserved renal function and stable haemodynamics, accompanied by close post-discharge follow-up. Decisions should remain individualised, especially for frail patients or those with advanced renal dysfunction or hypotension.
Beyond the statistical results, the trial underscores a shift in clinical perspective – hospitalisation should be viewed not only as a time for acute stabilisation, but also as an opportunity to initiate disease-modifying therapy during a period of high risk and high therapeutic yield. Early initiation of SGLT2 inhibitors ensures patients are discharged already receiving effective treatment, thereby reducing therapeutic inertia and the risk of early readmission.3,4
In conclusion, although neutral for its primary endpoint, DAPA ACT HF-TIMI 68 provides consistent efficacy and safety signals.1 Together with meta-analytic evidence, the findings suggest that early in-hospital initiation of dapagliflozin may improve outcomes during the vulnerable post-discharge phase. The data support its early integration into HF care with an individualised and cautious approach.